Optically active β-amino acids and derivatives thereof are useful chiral building blocks in organic synthetic chemistry, especially medicinal synthetic chemistry.
One useful synthesis method for the optically active β-amino acids and derivatives thereof is asymmetric Mannich reaction. One example of the asymmetric Mannich reaction is presented in the following Scheme 1.

In the asymmetric Mannich reaction, as presented in the above Scheme 1, use of a base and a metal (M+) deprotonates a carbonyl compound where a hydrogen atom is bonded to carbon at the α-position relative to the carbonyl carbon, to thereby form an enolate which is an active intermediate. Furthermore, by reacting the enolate with an imine which is an electrophile, a carbon-carbon bond is formed to obtain an optically active β-amino acid derivative having two asymmetric points. Here, when the base and the metal are used in amounts equal to or more than the amount of a starting material, the reaction becomes an equivalent reaction. When they are used in catalytic amounts, the reaction becomes a catalytic reaction.
20% or more of the currently sold pharmaceutical products contain at least one fluorine atom (see, for example, NPL 1). Therefore, a fluorine atom is desirably contained also in the optically active β-amino acids and derivatives thereof, which are synthesis intermediates of pharmaceutical products and useful chiral building blocks.
In the asymmetric Mannich reaction, when “C” is a usual alkyl group, the reaction of the Scheme 1 proceeds. When “C” is a CF3 group, however, β-elimination, which is a side reaction, preferentially proceeds as presented in the following Scheme 2. This raises a problem that the yield rate of a desired optically active 3-amino acid derivative considerably decreases.

Various studies have been made on the Mannich reaction using a carbonyl compound where a CF3 group is bonded to carbon at the α-position relative to the carbonyl carbon (see, for example, NPLs 2 to 5). In these studies, however, there are problems such as being a racemic synthesis, use of reagents more than equivalent amounts, and consumption of a large amount of optically active compounds by using chiral auxiliary groups.
Therefore, at present, there is a demand for providing a method for producing an optically active α-trifluoromethyl-β-amino acid derivative, the method being able to synthesize the optically active α-trifluoromethyl-β-amino acid derivative at high yield and catalytically without necessitating activating reagents more than equivalent amounts.